This invention relates to protecting against bacterial infection.
Traditional immunological models posit two classes of immune response: 1) the cellular immune responses mediated by lymphocytes designated as T cells which act directly against foreign matter or which activate macrophages to act against foreign matter; and 2) the humoral immune response initiated by a second class of lymphocytes designated as B cells. The cellular response involves direct attack by sensitized T cells on the invading antigen, e.g., attack on the surface of a foreign cell resulting in cell lysis. The humoral response involves secretion of antibodies by sensitized B cells. There are several other types of T cells in addition to the above-described cytotoxic T cells, including T cells that aid B-cell differentiation and proliferation (helper T cells), T cells that amplify cytotoxic T cells (T.sub.A cells), and T cells that suppress immune responses (suppressor T cells).
Much attention has been paid to antibody production by B cells, and it has become standard practice to generate antibodies to a selected antigen using hybrid cells made by fusing a sensitized B cell to a myeloma cell (B cell tumor line) that confers immortality on the hybrid.
It has also been known that an immune protection to pathologic bacteria or characteristic surface features of such bacteria can be transferred from one individual or species to another.
Ziegler et al. (1982) N.E. J. Med. 307:1225-1230 report treating human patients with human antiserum to bacterial endotoxin (lipopolysaccharide) prepared by vaccinating humans with heat killed Escherichia coli J5, a mutant having a core identical to most gram negative bacteria and lacking lipopolysaccharide oligosaccharide side chains.
An immune response to the capsular polysaccharide of Bacteroides fragilis protects against abscess formation caused by that organism. That immune response is reported to be cellular in nature, rather than humoral, and the cells that mediate the response are reportedly antigen-specific but non-H-2-restricted T cells belonging to the Ly-1.sup.- 2.sup.+ subset, a subset which would not be expected to include helper T cells. Shapiro et al. (1982) J. Exper Med. 154:1188-1197. Thus, Shapiro et al. say (at pp. 1195) that
It is not known how the protective effect against B. fragilis abcesses is mediated, but antibody production does not appear to play a decisive role . . . One might speculate that the immune T cell population is composed of suppressor cells . . . [A]nother possible interpretation is that T cells prevent the bacteria from becoming established at all . . . [An effector] T cell could function by binding or inactivating the bacteria or (more likely) by releasing a lymphokine that activates or attracts macrophages.
The protection against B. fragilis can be passively transferred by nylon wool non-adherent spleen cells. Onderdonk et al. (1982) J. Clin. Invest. 69:9-16.
Suppressor T cells are known to produce soluble factors specific for molecular antigens, and those soluble factors interact with other cells to control an immune response. Asherton et al. (1982) Annals. N.Y. Acad. Sci. Vol. 392:71-89. Healy et al. (1983) J. Immunology 131:2843-2847 disclose a suppressor T-cell hybridoma. Lifshitz et al. disclose a helper T-cell factor (1983) Proc. Nat'l Acad. Sci. 80:5689-5693. Murphy et al. (1983) J. Immunol. 130:2876-2881 disclose a soluble factor produced by antigen-specific suppressor T cells.